Redox‐regulation of haemostasis in hypoxic exercising humans: a randomised double‐blind placebo‐controlled antioxidant study

Abstract

In vitro evidence suggests that blood coagulation is activated by increased oxidative stress although the link and underlying mechanism in humans have yet to be established. We conducted the first randomised controlled trial to examine if oral antioxidant prophylaxis alters the haemostatic responses to hypoxia and exercise. Healthy males were randomly assigned double-blind to either an antioxidant (n = 20) or placebo group (n = 16). The antioxidant group ingested two capsules/day that each contained 500 mg of l-ascorbic acid and 450 international units (IU) of dl-α-tocopherol acetate for 8 weeks. The placebo group ingested capsules of identical external appearance, taste and smell (cellulose). Both groups were subsequently exposed to acute hypoxia and maximal physical exercise with venous blood sampled pre-supplementation (normoxia), post-supplementation at rest (normoxia and hypoxia) and following maximal exercise (hypoxia). Systemic free radical formation (electron paramagnetic resonance spectroscopic detection of the ascorbate radical (A )) increased during hypoxia (15,152 ± 1193 AU vs. 14,076 ± 810 AU at rest, P < 0.05) and was further compounded by exercise (16,569 ± 1616 AU vs. rest, P < 0.05), responses that were attenuated by antioxidant prophylaxis. In contrast, antioxidant prophylaxis increased thrombin generation as measured by thrombin-antithrombin complex, at rest in normoxia (28.7 ± 6.4 vs. 4.3 ± 0.2 μg mL pre-intervention, P < 0.05) and was restored but only in the face of prevailing oxidation. Collectively, these findings are the first to suggest that human free radical formation likely reflects an adaptive response that serves to maintain vascular haemostasis.

The interactive effects of acute exercise and hypoxia on cognitive performance: A narrative review

“…There are other candidates that potentially impair cognitive performance during prolonged exposure to hypoxia. First, free radical formation increases under hypoxia . It has recently been suggested that systemic oxidative‐inflammatory‐nitrosative stress in high‐altitude residents is associated with accelerated cognitive decline .…”

“…First, free radical formation increases under hypoxia. 88,89 It has recently been suggested that systemic oxidative-inflammatory-nitrosative stress in high-altitude residents is associated with accelerated cognitive decline. 90 Furthermore, peripheral blood hypersensitive C-reactive protein, which is a biomarker of inflammation, is correlated with cognitive impairments during high-altitude expeditions.…”

To clot or not to clot? That is a free radical question

“…That is, a probable increase in systemic free radicals, as supported by an increase in the VC radical, restored thrombin levels (Fall et al . ). The authors suggest that systemic free radical production is a hormetic phenomenon that contributes to physiological vascular haemostasis.…”

“…In an article in this issue of The Journal of Physiology , Fall et al . () provide novel insight regarding the redox regulation of haemostasis in vivo in the exercising human.…”

“…To investigate the redox regulation of haemostasis, Fall et al . () recruited 40 young healthy males and deployed a double‐blind placebo‐controlled nutritional antioxidant experimental design. The experimental design included three phases: (1) passive baseline testing in normoxia followed by 8 weeks of vitamin C (VC) and vitamin E (VE) supplementation; (2) post‐supplementation involving repeated baseline testing; and (3) a redox challenge phase consisting of passive hypoxia for 6 h at 12% O 2 before active hypoxia wherein participants completed an incremental exercise test at 12% O 2 .…”